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PubMed1994

Melanocytic nevi in children. I. Anatomic sites and demographic and host factors.

A survey of benign melanocytic nevi was conducted among schoolchildren in Perth, Western Australia, in 1985, with the aim of describing the prevalence and causes of nevi. Children were recruited from Perth public schools that were chosen to be representative of the socioeconomic and geographic distribution of the population. Of 4,898 eligible children, 2,595 (53%) had all of their nevi counted by one member of a team of five nurses. Analysis was restricted to 2,552 children aged 5-14 years. Children of European origin (i.e., white children), who comprised the majority of the sample (2,376 children), had many more nevi than did children of other ethnic origins. Among white children, the prevalence of nevi increased progressively with age, although the number of nevi per unit of skin area reached a plateau at about 9 years of age. Boys had more nevi at all ages than did girls. The number of nevi per unit of area was highest on the lateral surfaces of the upper limbs and the face and neck, and was lowest on the lower limbs. Children whose parents had been born in Southern Europe were likely to have few nevi. Children with red hair had relatively few nevi, but children with light skin generally had more nevi than children with darker skin. Ability to tan and propensity to burn were also associated with number of nevi, although not in a simple fashion; numbers of nevi were highest in intermediate categories of these two variables. The relation with freckling was also complex; the mean number of nevi increased with increasing freckling until the freckling became moderate to heavy, after which it fell.

Adolescent↗
PubMed2007

Common melanocytic nevi in 7-year-old schoolchildren residing at different latitudes in Sweden.

BACKGROUND: Current epidemiologic research shows consistently that increased number of acquired common melanocytic nevi (CMN) is an important risk factor for cutaneous malignant melanoma. The purpose of this study was to investigate the number of CMN in relation to tanning habits and complexion among 7-year-old children residing at different latitudes in Sweden. METHODS: Two municipalities were chosen at latitude 65 degrees N to 68 degrees N in the north of Sweden and two at latitude 57 degrees N in the south. Children born in 1994 and registered in the municipalities were to be included (N = 1,676). A questionnaire was sent to their parents asking about the child's tanning habits. A body examination of CMN of size >or=2 mm was done by the same trained nurse in 1,380 (82.3%) of the children. RESULTS: CMN was significantly less prevalent among children living in the north with a prevalence of 5.6 [95% confidence interval (95% CI), 4.8-6.5] inland and 6.2 (95% CI, 5.3-7.2) coastal compared with the south with a prevalence of 9.5 (95% CI, 8.2-11.0) inland and 10.4 (95% CI, 8.9-12.0) coastal. In addition, blond hair, blue/gray/green eyes, holidays at seaside resorts abroad, more frequent sunburns, and parents fancying tanning were significant predictors of higher prevalence of CMN. CONCLUSIONS: These findings support previous evidence that the development of CMN is related to the level of sun exposure in childhood expressed as latitude of residence, holidays at seaside resort abroad, and number of sunburns. To reduce the incidence of cutaneous malignant melanoma, a change in attitude and behavior must start with young children and their parents.

Child↗
PubMed2003

Evolutionary genetics of the melanocortin-1 receptor in vertebrates.

The molecular genetic basis of adaptive change in phenotype is a major outstanding issue in evolutionary biology. Evolutionary change in coat and plumage color is a promising system for making progress in this field. Most notably, recent work on the molecular genetic basis of hair and feather color has identified several genes which are candidates for involvement in evolutionary color change in mammals and birds. We have investigated the evolution of one of these candidate genes, the melanocortin-1 receptor (MC1R) gene, in relation to changes in melanin distribution among a wide variety of primate species, and in bananaquits (Coereba flaveola), which are a classic case of melanic plumage polymorphism in birds. In primates, a role of the MC1R coding region in coat color evolution can be ruled out in several cases in which closely related species have drastically different distributions of eumelanin and/or pheomelanin. However, reconstruction of MC1R sequences over primate evolution shows the presence of mutations at important functional sites in several lineages. Most notably, the lion tamarins (Leontopithecus) show a striking pattern of MC1R evolution, including deletions and several nonconservative amino acid changes. In the bananaquit, an E92K substitution in the MC1R is strongly associated with melanism, and this is likely to be the causative mutation. Reconstruction of the evolution of bananaquit MC1R alleles shows that melanism is a derived trait in this species. These results confirm the utility of a candidate gene approach to color evolution in vertebrates and open the way for extensive future research.

Animals↗
PubMed1988

Malignant melanoma--profile of an epidemic.

Cutaneous malignant melanoma is occurring in epidemic proportions in the United States. To provide a profile of persons at risk and the epidemiologic features of malignant melanoma, we reviewed the records of 325 patients with cutaneous malignant melanoma seen at the University of Colorado Health Sciences Center between 1973 and 1983. Most patients had fair skin, brown or blonde hair, blue or green eyes, and had difficulty in suntanning. The majority of melanomas (72%) developed in preexisting nevi. In women, melanomas were most common on the extremities, and in men they occurred most frequently on the trunk, head or neck. The most frequently noted depth of invasion was Clark's level IV. At diagnosis, most of the patients (77%) were at stage I. We conclude that malignant melanoma constitutes a major disease problem in the western United States that is largely preventable with appropriate physician and patient education.

Adolescent↗
PubMed2004

Inter-relation between variables determining constitutional UV sensitivity in Caucasian children.

BACKGROUND/PURPOSE: Sensitivity to ultraviolet (UV) light is associated with phenotypic variables like iris or hair colour or freckling, which are all strongly inter-related. We assessed the pattern of association among these factors to construct a summary measure reflecting constitutional UV sensitivity in a simple one-dimensional score with sufficient discriminating power. METHODS: Information on iris and hair colour (3 and 4 categories, respectively), freckling (none vs. any) and the reaction to mid-day summer sunlight as an outcome (dichotomized into 'burn' and 'tan') was collected in a cross-sectional study among children at school enrollment in 1999 and 2000 in Göttingen, Germany (n=3765 with complete data). Chi-squared automatic interaction detector (CHAID) analysis and log-linear modelling was used to assess the pattern of mutual inter-relations. RESULTS: Hair colour turned out to be the factor most strongly associated with UV sensitivity. In case of blonde or brown hair (the most common phenotypes in our sample), the consideration of freckling further refined the classification system, whereas iris colour did not contribute additional information. The results of the CHAID and log-linear analyses suggest a simple five-point score capturing constitutional UV sensitivity. The discriminating power of this score was high in our sample, with the proportion of persons who burned ranging from 7.7 (lowest category) to 73% (highest category). CONCLUSION: The new scoring system summarized efficiently relevant information on individual constitutional UV sensitivity in our sample. Its further validation in independent studies comprising Caucasian children or adults is necessary to assess objectively its properties for future applications.

Child↗
PubMed1992

Use of host factors to identify people at high risk for cutaneous malignant melanoma .

OBJECTIVE: To determine which host characteristics are risk factors for cutaneous malignant melanoma in order to aim prevention and early detection programs at people at high risk. DESIGN: Case-control study. SETTING: Southern Ontario. SUBJECTS: The 583 case subjects were aged 20 to 69 years and had had malignant melanoma newly diagnosed between Oct. 1, 1984, and Sept. 30, 1986. The 608 control subjects were randomly selected from a list of residents in the study area and were stratum matched for age, sex and municipality. INTERVENTION: Through in-person interviews the interviewer ascertained exposure to putative external risk factors and assessed skin colour and number of nevi on the arm, and the subject reported his or her natural hair colour at age 20 years, eye colour, skin reaction to repeated sun exposure, and freckle and whole-body nevus densities. RESULTS: Although all the host factors mentioned were significantly associated with melanoma risk when considered separately, only hair colour, skin reaction to repeated sun exposure, and self-reported freckle and nevus densities remained significant after backward logistic regression analysis. The odds ratio for melanoma was estimated to be 10.7 in people who had many nevi compared with those who had none (95% confidence interval [CI] 6.6 to 17.4), 4.0 in people who had red hair compared with those who had black hair (95% CI 1.9 to 8.2), 1.9 in people who had many freckles compared with those who had none or few (95% CI 1.3 to 2.8) and 1.4 respectively in people who burned and had a subsequent increase in tan and those who burned and had no increase in tan after repeated sun exposure compared with those who did not burn [corrected]. CONCLUSIONS: Four risk factors for malignant melanoma have been identified. Prospective evaluation of their predictive value should be done. In the meantime, however, these factors should be used to identify people apparently at high risk for malignant melanoma, who can then be targeted for early detection and prevention programs.

Adult↗
PubMedDate not supplied

A comparison of risk factors for malignant melanoma, squamous cell carcinoma and basal cell carcinoma in the UK.

Cutaneous malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) exhibit markedly different natural histories, but few studies have compared risk factors in individuals from a single population. Using logistic regression analysis in case and control groups, we assessed, the association of individual characteristics with MM (n = 240) and SCC (n = 184). We also compared differences in risk factors (eye/hair colour, skin type, smoking history, occupation, social class, tumour site) between MM/BCC and SCC/BCC. MM patients were more likely to have red/blonde hair and blue/green eyes than controls, and those with SCC more likely to have red/blonde hair, blue/green eyes, outdoor occupation, skin type 1 and to have smoked more. There were few differences in individual characteristics between the skin cancer groups, illustrating their non-specific nature. Tumour site, however, showed marked differences: MM patients were more likely to have a tumour on the trunk or limbs than BCC patients, while patients with SCC were more likely to have a tumour on the limbs. Reasons for this variation are unclear. The relatively weak effect of individual factors supports the view of a multifactorial disease and suggests that interactions between UV exposure and genetic predisposition may be more significant determinants of risk.

Adult↗
PubMed1996

Naevi and pigmentary characteristics as risk factors for melanoma in a high-risk population: a case-control study in New South Wales, Australia.

The relationship between risk of cutaneous malignant melanoma and total body and site-specific naevus counts and other host factors was investigated in a Caucasian population aged 15-84 years in New South Wales, Australia. The study sample comprised 244 cases with melanoma diagnosed in 1989-1993, and 276 controls. The strongest relationship was with total body naevus count. Risk of melanoma was raised 12 times in those with more than 100 naevi compared with those with less than 10. There were also strong risks, with odds ratios of 5 or more, associated with having multiple atypical naevi, multiple large naevi, high naevus counts in sun-exposed or sun-protected areas and being unable to tan on repeated sun exposure. The effect of inability to tan was stronger at younger than older ages. Lesser risks, with odds ratios of 2-3, were associated with being prone to burn on sun exposure, having many freckles as a child and having red hair. The site distribution of naevi in males compared with females resembled the distribution of melanoma by sex. Risk of melanoma of the back was significantly more closely related to back naevus count than naevus count for the remainder of the body. For other anatomical sites, naevus count was non-significantly more closely related to naevus counts at that site than counts over the remainder of the body. Naevus count declined with age in both cases and controls. In those aged under 40, having 100 or more naevi was associated with an aetiological fraction (AF) of 41%. In those aged 60 and over, however, the AF associated with this number of naevi was only 5%.

Adolescent↗
PubMed2005

Case-control study to identify melanoma risk factors in the Belgian population: the significance of clinical examination.

BACKGROUND: Although numerous studies have evaluated risk factors associated with cutaneous malignant melanoma (CMM), no such study has been carried out in Belgium. OBJECTIVES: To identify individuals who are at high risk of developing malignant melanoma in Belgium, which could enhance the efficacy of screening interventions and avoid unnecessary skin inspections. STUDY DESIGN/SETTING/SUBJECTS: We prospectively included patients who were diagnosed with invasive malignant melanoma between 1998 and 2001 at the Department of Dermatology in a case-control study. Controls were selected from the outpatient dermatology clinic. Participants were interviewed and clinically examined by a dermatologist. We asked questions concerning most known risk factors associated with malignant melanoma such as phenotypical and skin characteristics, and environmental and lifestyle exposures. To adjust for confounding variables and to estimate odds ratios (ORs) and 95% confidence intervals (CIs), a multivariate model was used. RESULTS: Although sunburn in childhood and substantial occupational solar exposure were modestly, but significantly, associated with malignant melanoma risk, clinical examination yielded several stronger risk factors. In a multivariate model, which adjusted for age, gender and skin phototype, phenotypical characteristics such as skin, hair and eye colour were significantly associated with the development of malignant melanoma. In the multivariate model, people with three or more atypical naevi were at more than 10-fold risk of developing a malignant melanoma (> or = 3 atypical naevi; adjusted OR = 11.40, 95% CI = 4.79-17.53) compared to those without an atypical naevus. The presence of one or more palpable naevi on the upper extremities or having solar lentigines increased the odds of developing malignant melanoma at least twofold. CONCLUSIONS: In Belgium, risk factors associated with malignant melanoma appear to be in accordance with previous studies. To assess peoples' risk profile, clinical skin examination is likely to yield the most important sporadic malignant melanoma risk factors. Therefore, focusing screening campaigns on individuals with predefined findings on skin self-examination may increase its efficacy.

Belgium↗
PubMed1996

The multicentre south European study 'Helios'. I: Skin characteristics and sunburns in basal cell and squamous cell carcinomas of the skin.

The aim of this study was to investigate constitutional and environmental determinants of non-melanocytic skin cancer among different populations from south Europe. Between 1989 and 1993 we interviewed incident cases and a random population sample of controls from five centres where a cancer registry was operating, whereas we selected a sample of hospital-based cases and controls from three other centres. Controls were stratified according to the age and sex distribution of cases. In all, 1549 cases of basal cell carcinoma (BCC), 228 of squamous cell carcinoma (SCC) and 1795 controls were interviewed. Both cancers affected primarily sun-exposed sites such as face, head and neck, but the prevalence of BCC on the trunk was higher than for SCC. Pigmentary traits such as hair and eye colour as well as tendency to sunburn were strong and independent indicators of risk for both BCC and SCC. In SCC, adjusted odds ratios (ORs) ranged from 1.6 for fair hair colour to 12.5 for red hair. Light-blonde hair entailed a risk of about 2 for BCC. Pale eye colour was associated with a risk of 1.8 for SCC and 1.4 for BCC. Subjects who always burn and never tan showed an adjusted OR of 2.7 for BCC and 2.0 for SCC. A history of sunburns and a young age at first sunburn were associated with an increased risk for BCC only (OR 1.7). Pigmentary traits and sun sensitivity of the skin confirmed their role as risk indicators. The effect of sunburns, as an indicator of both exposure and sun sensitivity of the skin, is less clear. Nevertheless, its association with BCC suggests, by analogy with melanoma, a relationship with intense sun exposure. Conversely, SCC would require prolonged exposure to sunlight.

Adolescent↗
PubMed1976

Staining of keratin and keratohyalin with the reactive dye levafix red violet E-2BL.

Demonstration of keratin in Zenker-fixed skin and in tissues stored in formalin can be difficult because such material is unsuitable for histochemical studies. A reactive dye, Levafix red violet E-2BL, proved useful for demonstration of keratohyalin and some types of keratin. Formalin-, Zenker- and methacarn-fixed sections were pretreated with alkaline alcohol, stained one hour at 60 C in an aqueous solution containing 0.25% Levafix red violet E-2BL plus 0.25% NaCl, rinsed in buffer solution pH 9, dehydrated and mounted. Keratohyalin granules and stratum corneum were colored red violet; hair and tonofibrils remained unstained. In sections prestained with Mayer's acid hemalum, keratohyalin was dark blue. Sulfonated monoazo dyes without reactive groups colored no tissue structures under the conditions of this technic; apparently, Levafix red violet E-2BL is bound via its reactive group. Polarization microscopic studies suggest binding of Levafix red violet E-2BL by an amorphous matrix of keratin. Correlations with chemical data indicate that the staining patterns parallel the distribution of proteins formed in the stratum granulosum.

Azo Compounds↗
PubMed1986

A rare case of numerous oral hairs in a 13-year-old boy with alopecia areata.

An extremely rare case of numerous oral hairs in a 13-year-old boy with alopecia areata is presented. The hairs growing from gingival pockets were black in color, similar to the hair on the patient's scalp. Microscopic examination of hairs from the oral cavity and those from the scalp showed differences in their structure.

Adolescent↗
PubMed2003

Genetic association and cellular function of MC1R variant alleles in human pigmentation.

We have examined MC1R variant allele frequencies in the general population of South East Queensland and in a collection of adolescent dizygotic and monozygotic twins and family members to define statistical associations with hair and skin color, freckling, and mole count. Results of these studies are consistent with a linear recessive allelic model with multiplicative penetrance in the inheritance of red hair. Four alleles, D84E, R151C, R160W, and D294H, are strongly associated with red hair and fair skin with multinomial regression analysis showing odds ratios of 63, 118, 50, and 94, respectively. An additional three low-penetrance alleles V60L, V92M, and R163Q have odds ratios 6, 5, and 2 relative to the wild-type allele. To address the cellular effects of MC1R variant alleles in signal transduction, we expressed these receptors in permanently transfected HEK293 cells. Measurement of receptor activity via induction of a cAMP-responsive luciferase reporter gene found that the R151C and R160W receptors were active in the presence of NDP-MSH ligand, but at much reduced levels compared with that seen with the wild-type receptor. The ability to stimulate phosphorylation of the cAMP response element binding protein (CREB) transcription factor was also apparent in all stimulated MC1R variant allele-expressing HEK293 cell extracts as assessed by immunoblotting. In contrast, human melanoma cell lines showed wide variation in the their ability to undergo cAMP-mediated CREB phosphorylation. Culture of human melanocytes of known MC1R genotype may provide the best experimental approach to examine the functional consequences for each MC1R variant allele. With this objective, we have established more than 300 melanocyte cell strains of defined MC1R genotype.

Alleles↗
PubMed2005

Maternal hair dye use and risk of neuroblastoma in offspring.

OBJECTIVE: Studies have suggested an association between maternal hair dye use and elevated risk of childhood cancer, including neuroblastoma. We analyzed data from a large case-control study to investigate the relationship between maternal hair dye use around pregnancy and risk of neuroblastoma in offspring. METHODS: Cases were children with neuroblastoma diagnosed between 1992 and 1994 at hospitals in the United States and Canada participating in the Children's Cancer Group or the Pediatric Oncology Group. Random-digit dialing was used to identify one matched control for each case. Information on hair dye use was gathered from telephone interviews of 538 case and 504 control mothers. RESULTS: Use of any hair dye in the month before and/or during pregnancy was associated with a moderately increased risk of neuroblastoma (adjusted odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.2-2.2). Temporary hair dye use (OR = 2.0, CI = 1.1-3.7) was more strongly associated with neuroblastoma than use of permanent hair dye (OR = 1.4, CI = 1.0-2.0). CONCLUSION: Although the results of this study provide evidence of an association between maternal hair dye use and neuroblastoma, further research is necessary to evaluate effects by method of hair dye application, color, and chemical composition.

Adult↗